Small interfering RNA-loaded chitosan hydrochloride/carboxymethyl chitosan nanoparticles for ultrasound-triggered release to hamper colorectal cancer growth in vitro
Copyright © 2020 Elsevier B.V. All rights reserved..
Development of nontoxic, targetable and potent small interfering RNAs (siRNA) delivery systems remains a predominant challenge for clinical application of siRNA therapy. The nanoparticles of carboxymethyl chitosan (CMC) and labeled fluorescein isothiocyanate (FITC)-chitosan hydrochloride (CHC) were fabricated as carriers for ultrasound-triggered drug delivery to treat colon cancer. The results showed the (FITC-CHC)-CMC nanoparticles could effectively encapsulate anti-β-catenin siRNA through ionic gelation self-assembly to improve the stability of siRNA. The cumulative release ratio of siRNA from crosslinked (FITC-CHC)-CMC nanoparticles was merely 11.08% in pH 2.2 solution within 120 min, whereas about 70.07% of the loaded siRNA was released within 120 min in pH 5.5 solution after an 8-min ultrasonic treatment. It indicated that the (FITC-CHC)-CMC based pH-sensitive delivery system could fulfill a controlled release of siRNA through responding to external stimulus (ultrasound) under favorable pH condition. Fluorescence microscopy measurements clearly visualized the entry of fluorescently-labeled siRNA into HT-29 cells. Following the transfection of anti-β-catenin siRNA for 48 h, the β-catenin protein expression of the colon cancer cells was reduced to about 40.10%, indicating effective reduction of the protein that promotes colon cancer proliferation. Our results demonstrated that the siRNA-(FITC-CHC)-CMC delivery system hold substantial potential for RNAi therapeutical applications in diseased cells.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:162 |
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| Enthalten in: |
International journal of biological macromolecules - 162(2020) vom: 01. Nov., Seite 1303-1310 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Yan, Ling [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 25.03.2021 Date Revised 25.03.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.ijbiomac.2020.06.246 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM311817467 |
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| 520 | |a Copyright © 2020 Elsevier B.V. All rights reserved. | ||
| 520 | |a Development of nontoxic, targetable and potent small interfering RNAs (siRNA) delivery systems remains a predominant challenge for clinical application of siRNA therapy. The nanoparticles of carboxymethyl chitosan (CMC) and labeled fluorescein isothiocyanate (FITC)-chitosan hydrochloride (CHC) were fabricated as carriers for ultrasound-triggered drug delivery to treat colon cancer. The results showed the (FITC-CHC)-CMC nanoparticles could effectively encapsulate anti-β-catenin siRNA through ionic gelation self-assembly to improve the stability of siRNA. The cumulative release ratio of siRNA from crosslinked (FITC-CHC)-CMC nanoparticles was merely 11.08% in pH 2.2 solution within 120 min, whereas about 70.07% of the loaded siRNA was released within 120 min in pH 5.5 solution after an 8-min ultrasonic treatment. It indicated that the (FITC-CHC)-CMC based pH-sensitive delivery system could fulfill a controlled release of siRNA through responding to external stimulus (ultrasound) under favorable pH condition. Fluorescence microscopy measurements clearly visualized the entry of fluorescently-labeled siRNA into HT-29 cells. Following the transfection of anti-β-catenin siRNA for 48 h, the β-catenin protein expression of the colon cancer cells was reduced to about 40.10%, indicating effective reduction of the protein that promotes colon cancer proliferation. Our results demonstrated that the siRNA-(FITC-CHC)-CMC delivery system hold substantial potential for RNAi therapeutical applications in diseased cells | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Carboxymethyl chitosan | |
| 650 | 4 | |a Chitosan hydrochloride | |
| 650 | 4 | |a Colon cancer | |
| 650 | 4 | |a Small interfering RNA | |
| 650 | 4 | |a Ultrasound | |
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| 650 | 7 | |a Drug Carriers |2 NLM | |
| 650 | 7 | |a RNA, Small Interfering |2 NLM | |
| 650 | 7 | |a carboxymethyl-chitosan |2 NLM | |
| 650 | 7 | |a Chitosan |2 NLM | |
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| 700 | 1 | |a Gao, Shengjie |e verfasserin |4 aut | |
| 700 | 1 | |a Shui, Shanshan |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Shuai |e verfasserin |4 aut | |
| 700 | 1 | |a Qu, Hao |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Changhong |e verfasserin |4 aut | |
| 700 | 1 | |a Zheng, Lei |e verfasserin |4 aut | |
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